Bone marrow-derived mesenchymal stem cells reduce brain amyloid-β deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model

BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:

2009

Contact PI Name:

Jae-sung Bae

Contact PI Affiliation:

Stem Cell Neuroplasticity Research Group, School of Medicine and Brain, Kyungpook National University, Daegu, South Korea

Co-Authors:

Jong Kil Lee, Hee Kyung Jin

Primary Reference (PubMED ID):

19084047

Funding Source:

Korea Science and Engineering Foundation (KOSEF)

Korean Ministry of Education, Science and Technology (MEST)

National Research Foundation of Korea (NRF)

Study Goal and Principal Findings:

The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) has recently been explored in various pathological conditions of the central nervous system (CNS). However, the application of BM-MSCs in acutely induced Alzheimer’s disease (AD) has not yet been reported. Herein the feasibility of using the BM-MSCs, as a therapeutic agent for AD has been tested. To assess this possibility, an acutely induced AD model induced by injecting amyloid-β (Aβ) into the dentate gyrus (DG) of hippocampus of C57BL/6 mice was used. Intracerebral transplantation of BM-MSCs into the brain of an induced AD model reduced their Aβ levels when compared to sham-transplanted animals. The diminution of Aβ deposits was accompanied by the activation of microglia. In addition, the activated microglia was located near the Aβ deposits, and their morphology was changed from ramified to ameboid as a sign of microglial phagocytosis. This study provides evidence that BM-MSCs can promote the reduction of Aβ through the microglial activation in this acutely induced AD brain, suggesting a potential therapeutic agent against AD.

Bibliographic Notes:

Hee Kyung Jin (College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea) and Jae-sung Bae (School of Medicine and Brain Korea 21, Kyungpook National University, Daegu, South Korea) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:

Therapy Type:

Biologic - Cell-based

Therapeutic Agent:

Mesenchymal Stem Cells (MSC)

PubMed

ClinicalTrials

Patents

Therapeutic Target:

Multi Target

Therapeutic Notes:

Bone marrow (harvested from 4- to 6-week-old C57BL/6 mice) cell-suspension cultures grown in stem cell medium for 2 weeks were used for all experiments.

Animal Model

Model Information:

Species:

Mouse

Model Type:

beta Amyloid Peptide Injection

Model Name:

C57BL/6 (beta Amyloid 1-42 Peptide Injection Model)

Strain/Genetic Background:

C57BL/6

Experimental Design

Is the following information reported in the study?:

Power/Sample Size Calculation

Randomized into Groups

Blinded for Treatment

Blinded for Outcome Measures

Pharmacokinetic Measures

Pharmacodynamic Measures

Toxicology Measures

ADME Measures

Biomarkers

Dose

Formulation

Route of Delivery

Duration of Treatment

Frequency of Administration

Age of Animal at the Beginning of Treatment

Age of Animal at the End of Treatment

Sex as a Biological Variable

Study Balanced for Sex as a Biological Variable

Number of Premature Deaths

Number of Excluded Animals

Statistical Plan

Genetic Background

Inclusion/Exclusion Criteria Included

Conflict of Interest

Outcomes

Outcome Measured

Outcome Parameters

Histopathology

beta Amyloid Deposits

Activated Microglia

Immunochemistry

Brain-beta Amyloid Deposits

Ionized Calcium Binding Adaptor Molecule 1 (Iba1)

Microscopy

Cell Count

Microglia Morphology

Cell Biology

Flow Cytometry

Outcomes Notes:

Flow cytometry was used to confirm integrity of Bone-Marrow derived Mesenchymal Stem Cell cultures by analyzing the expression levels of CD29, CD34, CD45, CD71, CD90, and CD117.

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